PHETA1 (also known as IPIP27A, Ses1, or FAM109A) is a PH domain-containing endocytic trafficking adapter protein essential for receptor recycling in the endosomal system 1. The protein localizes to early endosomes, recycling endosomes, and the trans-Golgi network, where it forms homo- and heterodimers required for directing recycled receptors both to the trans-Golgi network and back to the plasma membrane 1. PHETA1 functions by binding to OCRL1 (oculocerebrorenal syndrome of Lowe protein) and INPP5B via a conserved F&H motif, positioning it at critical junctions in endocytic trafficking 2. In vivo studies demonstrate that PHETA1 deficiency impairs endocytosis and ciliogenesis in renal tissues while disrupting craniofacial development through dysregulation of cathepsin K and abnormal collagen maturation 3. Disease relevance is underscored by a patient with the dominant-negative R6C variant exhibiting craniofacial defects, and by genetic evidence linking PHETA1 to primary open-angle glaucoma susceptibility, suggesting shared neuroprotective mechanisms in visual pathway tissues 43. These findings implicate PHETA1 dysfunction in Lowe syndrome and Dent disease pathogenesis, making it a potential target for therapeutic intervention in endosomal trafficking disorders.