ANKRD50 is a key component of the SNX27-retromer-WASH endosomal sorting complex essential for cargo recycling to the plasma membrane. 1 ANKRD50 mediates direct and cooperative interactions with multiple complex components, enabling efficient endocytic recycling of nutrient transporters including GLUT1 and SLC1A4. 1 Mechanistically, ANKRD50 depletion phenocopies loss of retromer or WASH function, resulting in mislocalization of cargo proteins. 1 Clinically, ANKRD50 has emerged as a disease-associated gene across multiple conditions. Upregulated ANKRD50 expression is identified as a plausible gastric cancer pathomechanism at a GWAS-identified risk locus. 2 Additionally, ANKRD50 harbors rare, probably damaging variants significantly enriched in Parkinson's disease patients compared to controls, making it a novel candidate PD gene. 3 Patients carrying multiple rare variants in PD-associated genes including ANKRD50 show higher disease risk and earlier age of onset. 3 ANKRD50 variants are also associated with lupus nephritis susceptibility. 4 These findings establish ANKRD50 as a functionally critical regulator of intracellular trafficking with relevance to neurodegeneration, cancer, and autoimmune disease pathogenesis.