PDZ domain-containing protein 8 (PDZD8)

PDZ domain-containing protein 8 (PDZD8) is a transmembrane protein found predominantly in the ER, containing an N-terminal transmembrane region, an SMP (Synaptotagmin-like, Mitochondrial lipid-binding Protein) domain, a PDZ protein interaction domain, a C1 lipid-binding domain, and a C-terminal coiled-coil domain[1][2][4][5]. PDZD8 tethers ER membranes to late endosomes and lysosomes through direct interaction with the small GTPase Rab7 and Protrudin, facilitating membrane contact site formation and lipid transport between organelles[1][5]. In neurons, PDZD8 is essential for ER-mitochondria tethering and regulates calcium dynamics via mitochondrial Ca²⁺ uptake[3][4]. It also promotes autophagy and lysosomal maturation, supporting synaptogenesis and axonal maintenance[2]. Loss-of-function mutations in PDZD8 have been implicated in intellectual disability and autism spectrum disorders[4]. PDZD8 has emerging roles in cancer biology, as increased expression may enhance cancer progression[3]. No drugs have been identified that directly target PDZD8, and it is not recognized as a clinical biomarker or therapeutic target.

Other names

PDZD8PDZK8bA129M16.2FLJ34427Sarcoma antigen NY-SAR-84/NY-SAR-104IDDADF