PDZK1, belonging to the Na+/H+ Exchanger (NHE) regulatory factor family, is a PDZ protein. It is involved in multiple biological functions and pathways. For example, it has a role in biomechanical-related chondrocyte biology, interacts with receptors like EGFR and PDGFR-β, and is associated with pathways such as PI3K/ERK2, STAT3/C-myc, and AKT/mTOR [1,2,3,4,5,6].

In OA, Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, suggesting that PDZK1 deficiency mediates excessive mechanical load-induced chondrocyte senescence and mitochondrial dysfunction [1]. In TNBC, downregulation of PDZK1 is related to erlotinib resistance, and it suppresses TNBC development by binding to EGFR and promoting its degradation [2]. In ccRCC, PDZK1 is downregulated in sunitinib-resistant specimens, and its low levels contribute to sunitinib insensitivity [3]. In glioma, knockdown of PDZK1 inhibits cell proliferation and invasion in vitro by inactivating the AKT/mTOR signaling pathway [6].

In conclusion, PDZK1 is crucial in various biological processes and disease conditions. Gene knockout models, especially in mice, have revealed its significant roles in OA, TNBC, ccRCC, and glioma. These findings provide insights into potential therapeutic strategies for these diseases by targeting PDZK1.