CHP2 (calcineurin like EF-hand protein 2) functions as a calcium-binding regulatory protein with dual roles in cellular homeostasis and cancer progression. The protein serves as an integral cofactor in pH regulation by controlling Na+/H+ exchanger activity, particularly NHE1 1. CHP2 undergoes calcium-induced conformational changes that modulate its interaction with NHE1, with calcium depletion decreasing binding affinity 7-fold compared to CHP1 1. In cancer, CHP2 is highly overexpressed in various malignancies including acute leukemia, breast cancer, and ovarian cancer, where it promotes tumor cell proliferation, invasion, and metastasis 234. The protein enhances cancer cell growth through AKT signaling activation and FOXO3a transcription factor suppression 3. CHP2 also facilitates G1-S phase cell cycle transition in breast cancer cells 3. Clinically, high CHP2 expression correlates with poor prognosis in breast cancer patients and serves as a potential prognostic marker in acute leukemia 32. Additionally, genetic variants in the CHP2 locus (rs109592) are associated with susceptibility to pulmonary Mycobacterium avium complex disease across multiple populations 5.