Mitochondrial autophagy (mitophagy) is the selective clearance of damaged or incomplete mitochondria by autophagy, which is critical for the functional integrity of the entire mitochondrial network and cell survival. Because dysfunction of mitophagy is closely related to many diseases, it is important to study the specific molecular mechanism and pathophysiological significance of mitophagy. FUN14 domain-containing 1 (FUNDC1) is a newly identified mitochondrial outer membrane protein that induces receptor-mediated mitophagy by its interaction with LC3 during hypoxia. The expression, phosphorylation, regulation and significance of FUNDC1 are reviewed in the context of a large number of pathophysiological conditions. Emerging evidence has demonstrated that levels and phosphorylation states of FUNDC1 are closely related to occurrence, progression and prognosis of various diseases including heart diseases and cancers, indicating that FUNDC1 may serve as a promising biomarker and potential therapeutic target.