NEBL (nebulette) encodes a cytoskeletal protein that functions as a structural component in muscle tissue, particularly in cardiac muscle thin filament assembly and Z disc organization 1. The protein exhibits actin filament binding activity and serves as a structural constituent of muscle, with roles in focal adhesion assembly. In cardiac pathophysiology, NEBL shows promoter hypomethylation and increased expression in dilated cardiomyopathy-associated heart failure, suggesting involvement in cardiac stress response mechanisms 1. NEBL has been implicated in sudden cardiac death syndromes, particularly dilated cardiomyopathy 2. In cancer biology, NEBL demonstrates complex, tissue-specific roles. In colorectal cancer, NEBL overexpression is associated with lymph node metastasis 3 and follows a gradual upregulation pattern in the mucosa-adenoma-carcinoma sequence 4, while paradoxically correlating with positive prognosis for overall survival 5. Conversely, in clear cell renal cell carcinoma, NEBL functions as a tumor suppressor, where downregulation promotes migration and invasion through epithelial-mesenchymal transition 6. Additionally, NEBL can form oncogenic fusion proteins with MLL in infant acute myeloid leukemia 7.