SMR3A (submaxillary gland androgen-regulated protein 3A) is a secretory protein physiologically expressed by salivary glands that belongs to a gene family producing opiorphin homologs 1. The protein may function in protection or detoxification processes and exhibits endopeptidase inhibitor activity. In cancer pathogenesis, SMR3A demonstrates context-dependent roles across different tumor types. In head and neck cancers, high SMR3A expression serves as an unfavorable prognostic marker, with strong expression found in 36% of oropharyngeal squamous cell carcinomas and correlating with poor progression-free and overall survival 2. The protein's expression is regulated by estrogen receptor 2 (ESR2) signaling, particularly in radioresistant head and neck squamous cell carcinoma cells, where fractionated irradiation leads to SMR3A accumulation 3. Conversely, adenoid cystic carcinomas show decreased SMR3A levels compared to normal glandular tissue 1. In breast cancer, SMR3A is among genes associated with lymph node metastasis and poor prognosis, with elevated expression linked to reduced overall survival in triple-negative breast cancer patients 45. The protein's role in prostate cancer involves promoting androgen-insensitive tumor growth and activating angiogenesis pathways 6.