Isoform 2 of Programmed cell death 6-interacting protein

Programmed cell death 6-interacting protein (PDCD6IP), also known as Alix, is a 96.8 kDa scaffolding protein encoded by PDCD6IP (UniProt: Q8WUM4-2). It functions as a multifunctional adaptor involved in protein trafficking, endosomal sorting, and apoptosis regulation, interacting with PDCD6 and other signaling partners to modulate cellular membrane dynamics and programmed cell death pathways.

PDCD6IP is widely expressed across tissues and plays roles in ESCRT-independent endosomal biogenesis and autophagy regulation. The protein localizes to endosomal and cytoplasmic compartments where it coordinates vesicular transport and protein cargo sorting. No specific genetic disease associations are documented in UniProt for this isoform.

In Alzheimer's disease, PDCD6IP isoform 2 is upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC = 0.86; Chaparral AD proteomics). This upregulation was detected across subcellular fractions in TMT-labeled mass spectrometry analysis of four compartments (P2, P3, S2, S3), suggesting increased PDCD6IP expression may relate to endosomal dysfunction and altered trafficking homeostasis characteristic of AD pathology.