C1orf115 (also known as RDD1, Required for Drug-induced Death 1) is a multi-functional regulator of drug efflux and lipid metabolism. Primary function: C1orf115 regulates drug efflux through modulation of ABCB1/MDR1 localization and activity 1, 2. Mechanism: The protein contains an N-terminal intrinsically disordered region and a C-terminal α-helix that binds phosphoinositides for plasma membrane localization 3. An acidic dileucine-like motif mediates interaction with the AP2 complex and clathrin-mediated endocytosis, a process essential for regulating drug resistance and modulated by acetylation 3. C1orf115 also induces ABCA1 transcription to promote cholesterol efflux in enterocytes 3. Disease relevance: Loss of C1orf115 confers resistance to multiple chemotherapy drugs 2, and low C1orf115 expression correlates with poor prognosis in colorectal cancer 4. Downregulation has been observed in Parkinson's disease 5 and may contribute to psychosis biotypes through RET and NCAM signaling pathways 6. Clinical significance: C1orf115 expression predicts treatment response to long-acting muscarinic antagonists in COPD patients 7. These findings suggest C1orf115 as a biomarker for chemotherapy sensitivity and potential therapeutic target for overcoming multidrug resistance.