SNX14 is a sorting nexin protein that functions as a critical regulator of intracellular lipid homeostasis and autophagosomal clearance. SNX14 localizes to the endoplasmic reticulum and functions in inter-organelle crosstalk, particularly between the ER, lysosomes, and lipid droplets 1. The protein binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes and lysosomes, and mediates autophagosome maturation and lysosomal fusion 2. Beyond autophagy, SNX14 acts as an interorganelle lipid transfer protein regulating lipid transport, lipid droplet biogenesis, and fatty acid desaturation 3. SNX14 additionally modulates GluA2 AMPA receptor degradation via the lysosomal pathway, influencing glutamatergic synaptic transmission 4. Loss of SNX14 function causes autosomal recessive spinocerebellar ataxia 20 (SCAR20), characterized by cerebellar neurodegeneration with cerebellar Purkinje cells showing selective vulnerability 3. Disease mechanisms involve disrupted lipid homeostasis with characteristic lipid storage defects, acylcarnitine accumulation, and lipotoxicity 3. Patients exhibit intellectual disability, cerebellar atrophy, and coarse facies 5. SNX14 therefore represents a key node integrating lipid metabolism with autophagy, with dysfunction causing primarily neurodegenerative disease.