Targeting melanosome pH is an effective method for the treatment of oculocutaneous albinism

Samuel J. Grondin; Daniela St. Pierre; David J Green; Sidra Amir; Maftuna Yusupova; Joseph Bonica; Zuhal Eraslan; Tyler Wills; Callum Hunt; Dalee Zhou; Aman George; Jaewon You; Aditya Anandakumar; S S Gross; Ryan P. Schreiner; Qiuying Chen; Mervyn George Thomas; Stacie K. Loftus; David R. Adams; Kazumasa Wakamatsu; Shosuke Ito; Panagiotis I. Sergouniotis; M E Harris; Brian P. Brooks; Jonathan Hale Zippin

doi:10.64898/2026.05.25.727673

PhysiologybioRxivMay 28, 2026

Preprint

Targeting melanosome pH is an effective method for the treatment of oculocutaneous albinism

Samuel J. Grondin, Daniela St. Pierre, David J Green, Sidra Amir, Maftuna Yusupova iD, Joseph Bonica, Zuhal Eraslan iD, Tyler Wills, Callum Hunt, Dalee Zhou iD, Aman George iD, Jaewon You iD, Aditya Anandakumar, S S Gross, Ryan P. Schreiner iD, Qiuying Chen iD, Mervyn George Thomas iD, Stacie K. Loftus iD, David R. Adams iD, Kazumasa Wakamatsu iD, Shosuke Ito iD, Panagiotis I. Sergouniotis iD, M E Harris, Brian P. Brooks iD, Jonathan Hale Zippin iD

Abstract

Oculocutaneous albinism (OCA) is a genetic condition associated with impaired visual acuity and increased skin cancer risk. When OCA is due to defects in melanosome ion transport, abnormally acidic conditions in the melanosome lumen inhibit tyrosinase, the critical pigment synthetic enzyme. Hence, a therapeutic approach that optimizes melanosome pH to increase pigment production presents a potential treatment for OCA and a method for decreasing skin cancer risk. Here, we report that reduction in sAC (ADCY10) activity via naturally occurring human variants in ADCY10 restores OCA pigmentation, and sAC inhibition increases melanin synthesis in both human and mouse OCA models. These findings demonstrate that targeting melanosome pH is an effective, previously untapped therapeutic strategy for OCA and elevated skin cancer risk.

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