PDZ domain containing 1 (PDZK1)

PDZ domain containing 1 (PDZK1) is a multi-PDZ domain scaffolding protein primarily involved in the regulation of epithelial cell membrane transporter function, especially in the kidney, intestine, and liver[5][6][7]. PDZK1 organizes protein complexes at the apical membrane by binding diverse partners, such as urate/anion exchangers (URAT1), organic ion transporters (OATs, OCTNs), peptide transporters (PEPT2), and the HDL receptor scavenger receptor class B type 1 (SCARB1)[5][6][7][8]. Through these interactions, PDZK1 controls transporter surface expression, localization, and activity, which in turn affects processes like ion exchange, cholesterol metabolism, and protein trafficking[6][7]. PDZK1 modulates the activity of CFTR (cystic fibrosis transmembrane conductance regulator) and is required for efficient brush border formation in kidney and intestinal cells[4][8][1]. It can suppress EGFR signaling in triple-negative breast cancer via specific PDZ domain interactions[2]. Genetic and functional studies link PDZK1 to metabolic syndrome, gout, cholesterol disorders, and cancer susceptibility[2][7]. There are no known drugs that directly target PDZK1, but its interactions influence the efficacy and activity of other drug targets, such as CFTR and EGFR[2][4][7].

Other names

Na(+)/H(+) exchange regulatory cofactor NHE-RF3NHERF3CAP70PDZD1CLAMPNaPi-Cap1CFTR-associated protein of 70 kDaSodium-hydrogen exchanger regulatory factor 3Na/Pi cotransporter C-terminal-associated protein 1PDZ-containing kidney protein 1

Scaffold-mediated modulation of transporter/receptor signaling, Regulates surface abundance and activity of binding partners (e.g., EGFR suppression, SCARB1 control, CFTR potentiation)[6][2][7]