MELK (maternal embryonic leucine zipper kinase) is a serine/threonine protein kinase belonging to the AMPK family that regulates multiple cellular processes including cell cycle progression, stem cell self-renewal, and apoptosis 1. The kinase phosphorylates diverse substrates including CDC25B (promoting mitotic checkpoint control), MAP3K5/ASK1 (activating apoptotic signaling), and BCL2L14 (inhibiting pro-apoptotic function) 2. In cancer biology, MELK promotes tumorigenesis through multiple mechanisms: it activates PI3K/mTOR signaling to enhance mitochondrial respiration and promote hepatocellular carcinoma (HCC) progression 3, and phosphorylates STAT3 to increase CCL2 expression, creating immunosuppressive microenvironments that reduce CD8+ T-cell infiltration and promote M2 macrophage polarization 4. MELK is frequently elevated in numerous cancer types and is classified as a hub gene in cervical cancer and psoriasis pathways 5. Clinically, MELK inhibition with small molecules like OTS167 and oleandrin impairs cancer cell proliferation, induces apoptosis, autophagy, and ferroptosis, and synergizes with radiotherapy to enhance antitumor immunity 46. However, controversy exists regarding MELK essentiality, as CRISPR-mediated knockout studies show conflicting results compared with RNAi and pharmacological approaches 2. Multiple MELK-targeting agents are under clinical development 7.