NSMAF (neutral sphingomyelinase activation associated factor) is a signaling adapter protein that couples TNF-receptor 1 (TNFR1) to neutral sphingomyelinase (N-SMase), regulating ceramide production in response to TNF-α 1. NSMAF functions as a scaffold protein that facilitates membrane trafficking events, including extracellular vesicle secretion through LC3-dependent autophagy pathways 12. The protein is part of the BEACH domain-containing protein family, which regulates lysosomal size and apoptosis through membrane dynamics 3. Clinically, NSMAF expression is dysregulated in multiple pathological contexts. In rotator cuff tendinopathy, NSMAF is expressed in injured tendons as part of the TNF-α signaling pathway, though expression levels vary substantially between patients 4. Genetic variations in NSMAF significantly influence pulmonary tuberculosis susceptibility in Moroccan populations, with specific SNPs associated with altered disease risk 5. NSMAF is also implicated in aneurysmal subarachnoid hemorrhage pathogenesis, functioning within NF-κB and sphingolipid signaling pathways 6. Additionally, microgravity exposure alters NSMAF expression in human fibroblasts, suggesting involvement in musculoskeletal pathology 7. These findings establish NSMAF as a critical mediator linking TNF signaling to inflammatory and degenerative diseases.