Melanoma differentiation-associated protein 5 (MDA5), acting as a widely expressed cytosolic pattern recognition receptor, plays a pivotal role in bridging innate and adaptive immune responses as well as mediating chronic tissue damage. Its autoantibody serves as a specific serological biomarker for the diagnosis of clinically amyopathic dermatomyositis (CADM). This article briefly introduces the basic and clinical research progress targeting MDA5 and anti-MDA5 antibodies in recent years, aiming to provide references for the development of precise intervention strategies for related diseases.