HPS5 is a component of the biogenesis of lysosomal organelles complex 2 (BLOC-2), essential for biogenesis of lysosome-related organelles (LROs) including melanosomes and platelet dense granules 1. HPS5 regulates intracellular vesicular trafficking and melanosome assembly, functioning as part of a multi-protein complex critical for proper protein trafficking to specialized organelles 2. The protein works coordinately with other BLOC complexes and AP-3 to maintain ion homeostasis within LROs; disruption of HPS5 leads to impaired trafficking of zinc transporters and accumulation of intracellular zinc, ultimately compromising dense granule biogenesis 3. Mutations in HPS5 cause Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, pigmentation defects in melanosomes, and platelet storage pool deficiency with bleeding tendency 4. HPS5 mutations present with hypopigmentation, photophobia, and ocular manifestations, with some patients experiencing additional systemic complications 5. The clinical severity can vary, with recent findings demonstrating that synonymous and intronic variants causing alternative splicing represent pathogenic mechanisms 4. Animal models validate HPS5's role, as mutations in Drosophila and stickleback orthologues produce similar pigmentation defects 16.