MIS18A is a kinetochore protein essential for centromere maintenance and accurate chromosome 21. Its primary function is recruiting CENP-A, a histone H3 variant that epigenetically defines centromeres, to centromeric chr21 1. MIS18A operates as part of the Mis18 complex (Mis18α-Mis18β-Mis18BP1), which must be activated during early G1 phase to restore CENP-A nucleosomes diluted during DNA replication 2. PLK1 phosphorylates MIS18A at Ser54, enabling PLK1 binding through its Polo-box domain and activating the complex to facilitate HJURP-mediated CENP-A loading 1. Additionally, SUMO polymer regulation by SENP6 controls MIS18A modification, necessary for proper centromere-associated network assembly 3. Beyond centromere function, MIS18A expression is developmentally regulated. In Down syndrome models, MIS18A overexpression inhibits Sonic hedgehog-dependent proliferation of granule cell precursors, suggesting dosage-sensitive effects on developmental signaling 4. MIS18A expression is also cell cycle-regulated and downregulated by Fam72a during mitogen stimulation, influencing neural stem cell proliferation 5. As a stemness-associated gene, MIS18A has been identified as a potential biomarker in acute leukemia studies 6. These findings establish MIS18A as critical for both centromere biology and developmental/pathological cell cycle control.