ACADS (acyl-CoA dehydrogenase short chain) encodes a mitochondrial enzyme catalyzing the first step of short-chain fatty acid β-oxidation, specifically dehydrogenating acyl-CoAs with 4-6 carbon saturated chains to form trans-2-enoyl-CoA intermediates 12. This process is essential for energy production from fats and occurs within the mitochondrial matrix 3. ACADS functions alongside related dehydrogenases (HADHA, HADHB, ECHS1) in coordinated fatty acid catabolism 3. Short-chain acyl-CoA dehydrogenase deficiency (SCADD), caused by biallelic ACADS variants, represents a rare inborn error of metabolism detected through newborn screening via elevated C4-acylcarnitine 45. Population studies reveal SCADD incidence of approximately 1/30,649 in eastern China 5, with ethnic clustering in Slovak Roma populations 4. However, clinically ascertained patients show variable presentations—ranging from asymptomatic detection to hypotonia, motor delay, and cyclic vomiting 6—while unselected population studies demonstrate that carriers of both rare and common ACADS variants lack documented metabolic disease 7. Recently, ACADS emerged as a potential tumor suppressor in colorectal cancer, where downregulation correlates with poor prognosis 8. ACADS suppresses cancer cell proliferation through ROS-triggered autophagy and CDK2 degradation, establishing ACADS-autophagy as a negative axis of cancer progression 8.