ZFYVE26 (SPASTIZIN) is a phosphatidylinositol 3-phosphate-binding protein that plays critical roles in autophagy and endolysosomal trafficking 1. The protein is required for autophagosome maturation, as mutations in ZFYVE26 lead to accumulation of immature autophagosomes and increased levels of autophagy markers MAP1LC3B-II and SQSTM1/p62 1. ZFYVE26 associates with the AP5 (adaptor protein complex 5) and functions in autophagic lysosomal reformation 2. The protein interacts with RAB5A and RAB11, key regulators of endosome trafficking, and acts at the intersection between autophagy and endocytosis 2. Loss of ZFYVE26 function causes hereditary spastic paraplegia type 15 (SPG15), an autosomal recessive neurodegenerative disorder characterized by progressive spasticity, cerebellar ataxia, cognitive decline, and thinning of the corpus callosum 3. Disease onset typically occurs in early childhood with developmental delays preceding motor symptoms 3. Mouse models demonstrate that ZFYVE26 deficiency leads to accumulation of lysosomal deposits in neurons and progressive loss of cortical motoneurons and Purkinje cells, confirming that endolysosomal dysfunction underlies SPG15 pathogenesis 4. Elevated plasma neurofilament light chain levels serve as biomarkers of neuroaxonal injury in affected patients 5.