NACAD (NAC alpha domain containing) is a cytoplasmic protein that functions in protein targeting regulation. Based on sequence similarity, NACAD may prevent inappropriate ER targeting of non-secretory polypeptides by binding nascent polypeptide chains as they emerge from the ribosome and blocking their interaction with the signal recognition particle (SRP), which normally directs secretory peptides to the ER. It may also reduce ribosomal affinity for ER membrane translocation sites. Clinically, NACAD has emerged as a novel metastasis-related protein in nasopharyngeal carcinoma, with NACAD knockdown dramatically enhancing cell migration and invasion 1. In glioblastoma multiforme, NACAD was identified as an independent prognostic factor for overall and disease-specific survival within a competitive endogenous RNA regulatory network 2. NACAD also appears relevant to breast cancer prognosis, being identified among 11 candidate prognostic genes in a CXCL12-related signature 3. Additionally, a rare NACAD deletion on chromosome 7 was identified in brothers with COVID orchitis, suggesting potential genetic susceptibility involvement 4. NACAD deletions have been documented as part of larger genomic rearrangements associated with cerebral cavernous malformations, though heterozygous deletion appears phenotypically silent 5, 6.