GNPTAB encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase, a Golgi apparatus enzyme catalyzing the phosphorylation of high-mannose oligosaccharides with mannose-6-phosphate (M6P) markers 1. M6P residues serve as critical recognition signals enabling mannose-6-phosphate receptor (MPR)-mediated vesicular transport of soluble lysosomal enzymes from the Golgi to endosomal/prelysosomal compartments 2. Loss of GNPTAB function results in impaired lysosomal enzyme trafficking and depletion of lysosomal hydrolases, compromising cellular degradative capacity 2. Mutations in GNPTAB cause mucolipidosis (ML) II and ML III alpha/beta, rare autosomal recessive lysosomal storage disorders characterized by skeletal deformities, developmental delay, and shortened lifespan 3. ML II patients exhibit median survival of 5.0 years with frequent pulmonary and cardiac complications, while ML III typically shows prolonged survival (median 62.0 years) 3. Beyond lysosomal storage disease, GNPTAB dysfunction impairs regenerative responses in differentiated cells by disrupting mTORC1-mediated proliferation and metaplasia-associated gene expression 4, and astrocyte-specific GNPTAB deficiency causes speech-related vocalization deficits in animal models of human stuttering 5. Additionally, GNPTAB mutations enhance alpha-synuclein neurotoxicity, implicating this gene in Parkinson's disease pathogenesis 6.