SAMM50 is a critical component of the mitochondrial sorting and assembly machinery (SAM) complex that maintains mitochondrial structure and function. Its primary role involves regulating cristae architecture and assembly of respiratory chain complexes 12, with required participation in TOMM40 incorporation into the TOM complex 3. Mechanistically, SAMM50 operates through multiple pathways: it interacts with the MICOS complex and ATAD3 to preserve mtDNA stability and integrity 4, requires N-myristoylation for proper mitochondrial targeting and protein-protein interactions with MIC19 5, and acts as a mitophagy receptor through direct interaction with ATG8 and p62/SQSTM1 to mediate quality control of SAM and MICOS components 6. Functionally, SAMM50 cooperates with Mic60 to bind cardiolipin, maintaining membrane integrity; its depletion triggers cardiolipin externalization, leading to mitochondrial remodeling and mtDNA release 4. Disease relevance is evident in liver pathology: SAMM50 genetic variants associate with non-alcoholic fatty liver disease (NAFLD) development and severity in both pediatric and adult populations 789, and acetaminophen-induced SAM50 reduction activates mtDNA-dependent innate immunity causing hepatotoxicity 4. Additionally, SAMM50 participates in mitochondrial responses to pathogenic stress, including Toxoplasma infection 10.