WDR83 (also known as MORG1) is a WD-repeat molecular scaffold protein with multifaceted cellular functions. Functionally, WDR83 acts as a scaffold linking ERK pathway responses to specific agonists, with biphasic dose-dependent effects on ERK activation 1. WDR83 regulates pre-mRNA splicing by interacting with spliceosomal components 1, and participates in tight junction development by coordinating PAR6-aPKC translocation to regulate apico-basal polarity. Mechanistically, WDR83 negatively regulates mTORC1 signaling under nutrient-rich conditions by binding active RRAG GTPases to prevent lysosomal recruitment of mTORC1, thereby facilitating constitutive basal autophagy 2. WDR83 also acts as a negative regulator of HIF-1α by interacting with prolyl-hydroxylase 3 (PHD3), promoting HIF-1α degradation under normoxic conditions 34. Disease relevance includes roles in cancer pathogenesis, where WDR83 upregulation correlates with gastric cancer progression through bidirectional regulation with DHPS 5, and dysregulation of basal autophagy increases cancer cell proliferation and migration 2. Clinically, WDR83 haploinsufficiency and missense variants are associated with neurodevelopmental disorders, intellectual disability, and sporadic ADHD 67, with the p.L218P variant disrupting neuronal morphogenesis and dendritic development.