Tyrosine-protein phosphatase non-receptor type 23

PTPN23 is a tyrosine-protein phosphatase that participates in endocytic cargo sorting by interacting with the ESCRT-I complex to direct ubiquitinated proteins into multivesicular bodies; it may also negatively regulate Ras-mediated signaling and contribute to ciliogenesis (UniProt: Q9H3S7). The protein is broadly expressed and has been associated with neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity (NEDBASS), an autosomal recessive condition characterized by developmental delay, ventriculomegaly, brain atrophy, and intellectual disability. In Alzheimer's disease, PTPN23 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.89), as measured by quantitative proteomics across subcellular fractions (Chaparral AD proteomics). This down-regulation may reflect disrupted endosomal sorting and ESCRT function in neurodegeneration.