SCHEDULE 13G Amendment No. 0 PROTEOSTASIS THERAPEUTICS INC COMMON STOCK Cusip #74373B109 Check the appropriate box to designate the rule pursuant to which this Schedule is filed: [ ] 	 Rule 13d-1(b) [x] 	 Rule 13d-1(c) [ ] 	 Rule 13d-1(d) Cusip #74373B109 Item 1: 	 	Reporting Person - FMR LLC Item 2: 	 	(a) 	[ ] 	 	(b) 	[ ] Item 4: 	 	Delaware Item 5: 	 	1,877,812 Item 6: 	 	0 Item 7: 	 	1,877,812 Item 8: 	 	0 Item 9: 	 	1,877,812 Item 11: 	 	9.825% Item 12: 	 	HC Cusip #74373B109 Item 1: 	 	Reporting Person - Abigail P. Johnson Item 2: 	 	(a) 	[ ] 	 	(b) 	[ ] Item 4: 	 	United States of America Item 5: 	 	0 Item 6: 	 	0 Item 7: 	 	1,877,812 Item 8: 	 	0 Item 9: 	 	1,877,812 Item 11: 	 	9.825% Item 12: 	 	IN Item 1(a). 	 	Name of Issuer: 	 	 	PROTEOSTASIS THERAPEUTICS INC Item 1(b). 	 	Address of Issuer's Principal Executive Offices: 	 	 	200 Technology Square, 4th Floor 	 	 	Cambridge, MA 02139 	 	 	USA Item 2(a). 	 	 Name of Person Filing: 	 	 	 FMR LLC Item 2(b). 	 	 Address or Principal Business Office or, if None, Residence: 	 	 	 245 Summer Street, Boston, Massachusetts 02210 Item 2(c). 	 	 Citizenship: 	 	 	 Not applicable Item 2(d). 	 	 Title of Class of Securities: 	 	 	 COMMON STOCK Item 2(e). 	 	 CUSIP Number: 	 	 	 74373B109 Item 3. 	 	Not Applicable Item 4. 	 	Ownership 	 	 	(a) Amount Beneficially Owned: 	1,877,812 	 	 	(b) Percent of Class: 	9.825% 	 	 	(c) Number of shares as to which such person has: 	 	 	 (i) sole power to vote or to direct the vote: 1,877,812 	 	 	 (ii) shared power to vote or to direct the vote: 	0 	 	 	 (iii) sole power to dispose or to direct the disposition of: 	1,877,812 	 	 	 (iv) shared power to dispose or to direct the disposition of: 	0 Item 5. 	 	Ownership of Five Percent or Less of a Class. 	 	 	Not applicable. Item 6. 	 	Ownership of More than Five Percent on Behalf of Another Person. 	 The interest of one person, F-Prime Capital Partners Healthcare Fund II LP, in the COMMON STOCK of PROTEOSTASIS THERAPEUTICS INC, amounted to 1,877,812 shares or 9.825% of the total outstanding COMMON STOCK at February 17, 2016. Item 7. 	 	Identification and Classification of the Subsidiary Which Acquired the Security Being Reported on By the Parent Holding Company. 	 	 	See attached Exhibit A. Item 8. 	 	Identification and Classification of Members of the Group. 	 	 	Not applicable. Item 9. 	 	Notice of Dissolution of Group. 	 	 	Not applicable. Item 10. 	 	Certifications. By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect. Signature After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct. 	February 18, 2016 	Date 	/s/ Daniel T. Gallagher 	Signature 	Daniel T. Gallagher 	 Duly authorized under Power of Attorney effective as of November 30, 2015, by and on behalf of FMR LLC and its direct and indirect subsidiaries* * This power of attorney is incorporated herein by reference to Exhibit 24 to the Form 4 filed by FMR LLC on February 18, 2016, accession number: 0000315066-16-005625 Exhibit A Pursuant to the instructions in Item 7 of Schedule 13G, the following table lists the identity and Item 3 classification, if applicable, of each relevant entity that beneficially owns shares of the security class being reported on this Schedule 13G. Entity 	ITEM 3 Classification IMPRESA MANAGEMENT LLC * 	IA * Entity beneficially owns 5% or greater of the outstanding shares of the security class being reported on this Schedule 13G. Abigail P. Johnson is a Director, the Vice Chairman, the Chief Executive Officer and the President of FMR LLC. Members of the Johnson family, including Abigail P. Johnson, are the predominant owners, directly or through trusts, of Series B voting common shares of FMR LLC, representing 49% of the voting power of FMR LLC. The Johnson family group and all other Series B shareholders have entered into a shareholders' voting agreement under which all Series B voting common shares will be voted in accordance with the majority vote of Series B voting common shares. Accordingly, through their ownership of voting common shares and the execution of the shareholders' voting agreement, members of the Johnson family may be deemed, under the Investment Company Act of 1940, to form a controlling group with respect to FMR LLC. This filing reflects the securities beneficially owned, or that may be deemed to be beneficially owned, by FMR LLC, certain of its subsidiaries and affiliates, and other companies (collectively, the "FMR Reporters"). This filing does not reflect securities, if any, beneficially owned by certain other companies whose beneficial ownership of securities is disaggregated from that of the FMR Reporters in accordance with Securities and Exchange Commission Release No. 34-39538 (January 12, 1998). RULE 13d-1(k)(1) AGREEMENT The undersigned persons, on February 18, 2016, agree and consent to the joint filing on their behalf of this Schedule 13G in connection with their beneficial ownership of the COMMON STOCK of PROTEOSTASIS THERAPEUTICS INC at February 17, 2016. 	FMR LLC 	By /s/ Daniel T. Gallagher 	Daniel T. Gallagher 	Duly authorized under Power of Attorney effective as of November 30, 2015, by and on behalf of FMR LLC and its direct and indirect subsidiaries* 	Abigail P. Johnson 	By /s/ Daniel T. Gallagher 	Daniel T. Gallagher 	Duly authorized under Power of Attorney effective as of June 18, 2014, by and on behalf of Abigail P. Johnson* * This power of attorney is incorporated herein by reference to Exhibit 24 to the Form 4 filed by FMR LLC on February 18, 2016, accession number: 0000315066-16-005625