Re: Prothena Corporation plc (theCompany) Dear Sirs, We are acting as Irish counsel to the Company, a public limited company incorporated under the laws of Ireland (registered number 518146), in connection with the proposed equity offering of up to 2,250,000 ordinary shares, par value $0.01 per share (theInitial Shares), together with an option to subscribe for up to an additional 337,500 ordinary shares (theOption Shares, and together with the Initial Shares, theShares) pursuant to (i) a registration statement on Form S-3 filed by the Company, on 6 April 2015, with the U.S. Securities and Exchange Commission (theSEC) under the Securities Act of 1933, as amended (theSecurities Act) (theRegistration Statement); (ii) the base prospectus dated 6 April 2015 (theProspectus); (iii) a preliminary prospectus supplement filed with the SEC on 5 January 2016 (thePreliminary Prospectus Supplement) and (iv) a final prospectus supplement filed with the SEC on 7 January 2016 (theFinal Prospectus Supplement) (the Preliminary Prospectus Supplement and the Final Prospectus Supplement together, theProspectus Supplements). RBC Capital Markets, LLC, UBS Securities, LLC, Barclays Capital Inc., Oppenheimer & Co Inc., Wedbush Securities Inc., Ladenburg Thalmann & Co. Inc. and LifeSci Capital LLC (theUnderwriters) have acted as underwriters to this proposed primary equity offering, as documented in an underwriting agreement between the Company and RBC Capital Markets, LLC, UBS Securities, LLC and Barclays Capital Inc. (for themselves and as representatives of the Underwriters) dated 6 January 2016 (theUnderwriting Agreement) (the Underwriting Agreement, together with the Registration Statement, theTransaction). In connection with this Opinion, we have reviewed copies of such corporate records of the Company as we have deemed necessary as a basis for the opinions hereinafter expressed. In rendering this Opinion, we have examined, and have assumed the truth and accuracy of the contents of, such documents and certificates of officers of the Company and of public officials as to factual matters and have conducted such searches, as of the date hereof, in public registries in Ireland as we have deemed necessary or appropriate for the purposes of this Opinion but have made no independent investigation regarding such factual matters. In our examination we have assumed the (continued) truth and accuracy of the information contained in such documents, the genuineness of all signatures, the authenticity of all documents submitted to us as originals, the conformity to original documents of all documents submitted to us as certified or photostatic copies and the authenticity of the originals of such documents. We have further assumed that, at the time of the issuance of the Shares, a sufficient number of ordinary shares will be authorised and available for issuance and that the consideration for the issuance of such Shares will not be less than the par value of the ordinary shares, and that the Company’s board of directors (theBoard), or any appropriate committee appointed thereby, will have the valid authority to issue such Shares on a non pre-emptive basis. We have further assumed that none of the resolutions and authorities of the shareholders or directors of the Company upon which we have relied have been or will be varied, amended or revoked in any respect or have expired and that the Shares will be issued in accordance with such resolutions and authorities. We have assumed the absence of fraud on the part of the Company and its respective officers, employees, agents and advisers and that the Company will issue the Shares in good faith, for its legitimate and bona fide business purposes. We have further assumed that: (i) the Company will be fully solvent at the time of and immediately following the issue of any Shares; (ii) no resolution or petition for the appointment of a liquidator or examiner will be passed or presented prior to the issue of any Shares; (iii) no receiver will have been appointed in relation to any of | | 
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