CALML3 (calmodulin-like 3) functions as a tumor suppressor gene with roles in cell differentiation and proliferation control. In normal human skin, CALML3 is strongly expressed in differentiating keratinocyte layers, exhibiting peripheral localization in suprabasal cells and nuclear localization in the stratum granulosum 1. Nuclear CALML3 expression is inversely correlated with the proliferation marker Ki-67, indicating its association with terminal cell differentiation and post-mitotic state 1. CALML3 acts as a suppressor of metastasis in hepatocellular carcinoma, where loss of CALML3 predicts shorter overall and relapse-free survival in postoperative patients 2. The gene serves as a dynamic network biomarker that can indicate metastasis initiation at the tipping point before irreversible tumor progression 2. Additionally, CALML3 shows potential correlation with disease severity in late-onset Pompe disease, suggesting it may serve as a biomarker for this lysosomal storage disorder 3. The loss of nuclear CALML3 indicates progression to a proliferative and potentially malignant phenotype, making it a useful marker for distinguishing normal from transformed cellular states 1.