Cab39, also known as calcium-binding protein 39, is involved in multiple biological processes and signaling pathways. It has been implicated in regulating the phosphorylation and activation of the thiazide-sensitive NCC for sodium-potassium balance through the WNK-SPAK/OSR1-NCC pathway [4]. It also participates in the LKB1-AMPK-LC3 pathway, which is related to autophagy, and the NF-κB signaling pathway [1,3]. These pathways are crucial for maintaining cell homeostasis, and dysregulation of Cab39 can lead to various disease states.

In bladder cancer, knockdown of Cab39 in cisplatin-resistant cells made them more sensitive to cisplatin, indicating that Cab39 promotes cisplatin resistance through the LKB1-AMPK-LC3 pathway, enhancing autophagy to maintain mitochondrial health and reduce ROS levels [1]. In nasopharyngeal carcinoma CNE-1 cells, over-expression of Cab39 increased cell proliferation via up-regulating p-JNK [2]. In bladder cancer, shRNA-mediated Cab39 knockdown mitigated the oncogenic trajectory, reversing invasive and metastatic behaviors [3]. In the context of potassium-regulated kidney function, global knockout of Cab39l and tamoxifen-inducible, NCC-driven Cab39 knockout (Cab39-DKO) led to a loss-of-NCC function similar to Gitelman syndrome [4].

In summary, Cab39 is essential for multiple biological functions, especially those related to cell survival, proliferation, and ion balance. Studies using knockout models, such as the Cab39-DKO mice, have revealed its roles in diseases like bladder cancer, nasopharyngeal carcinoma, and kidney ion-regulation disorders. Understanding Cab39's functions provides insights into disease mechanisms and potential therapeutic targets.