ACTB (actin beta) is a highly conserved cytoskeletal housekeeping protein that polymerizes into filaments forming cross-linked networks throughout the cytoplasm 12. Both monomeric (G-actin) and polymeric (F-actin) forms regulate cell motility, contraction, and cytoskeletal organization 2. Beyond its cytoplasmic role, nuclear ACTB regulates gene transcription, DNA repair, and participates in gamma-tubulin ring complex assembly for microtubule nucleation 3. Heterozygous loss-of-function ACTB mutations cause a distinct developmental disorder characterized by intellectual disability, organ malformations (cardiac, renal), growth retardation, and facial dysmorphism 4. These mutations reduce nuclear ACTB levels, impairing cell proliferation and altering cell-cycle gene expression 4. Conversely, gain-of-function missense mutations cause Baraitser-Winter syndrome, presenting with intellectual disability, cortical malformations, coloboma, and deafness 5. In cancer biology, ACTB expression is frequently upregulated across multiple tumor types including liver, lung, breast, and colorectal cancers 6. Elevated ACTB correlates with poorer survival and metastasis specifically in hepatocellular carcinoma, head and neck squamous cell carcinoma, and lung adenocarcinoma 7. Abnormal ACTB polymerization promotes tumor invasiveness and metastatic potential 6. Additionally, ACTB serves as a reliable housekeeping gene for RT-qPCR normalization in various cell types, though suitability varies by cellular context 89.