ARSI (arylsulfatase family member I) is a member of the arylsulfatase protein family that displays sulfuric ester hydrolase activity. The protein localizes to the endoplasmic reticulum lumen and demonstrates arylsulfatase activity at neutral pH when co-expressed with SUMF1, with enzymatic activity detected in secretion medium of retinal cell lines 1. However, conflicting data indicate that ARSI may lack arylsulfatase activity under certain conditions 2. The gene is capable of protein binding and possesses sulfuric ester hydrolase activity as annotated in gene ontology databases. Clinically, ARSI should not be confused with androgen receptor signaling inhibitors (also abbreviated as ARSI), which are important therapeutic agents in prostate cancer treatment. These androgen receptor signaling inhibitors, including abiraterone and enzalutamide, have substantially advanced metastatic castration-resistant prostate cancer (mCRPC) treatment but are associated with increased cardiovascular toxicity including hypertension, acute coronary syndrome, and cardiac dysrhythmias 3. Genomic alterations identified in mCRPC patients receiving these therapies, such as RB1 mutations, significantly predict poor treatment outcomes 4. Homologous recombination repair gene alterations, particularly BRCA1/2 mutations, also correlate with worse survival outcomes in ARSI-treated mCRPC patients 5. The arylsulfatase protein's specific biological role in disease pathogenesis remains incompletely characterized.