MYLK (myosin light chain kinase) is a calcium/calmodulin-dependent kinase that plays critical roles in smooth muscle contraction and vascular integrity. The gene undergoes alternative splicing to produce functionally distinct variants, including nmMLCK2, which lacks exon 11 and is associated with reduced endothelial barrier integrity 1. Mechanical stress and genetic variants (SNPs rs77323602 and rs147245669) regulate this alternative splicing, with pathologic mechanical stress increasing nmMLCK2 expression 1. MYLK is implicated in heritable thoracic aortic disease (HTAD), where pathogenic variants contribute to aortic aneurysms and dissections 2. In aging-related aortic pathology, miR-1204 targets MYLK, leading to vascular smooth muscle cell senescence and loss of contractile phenotype, which aggravates aortic aneurysm and dissection formation 3. Copy number variations in MYLK, including intragenic deletions, have been identified as pathogenic variants in HTAD patients through next-generation sequencing panels 4. The gene is also associated with Marfan syndrome and related connective tissue disorders 5. Clinically, MYLK variants show gene-specific risks for aortic events, supporting personalized surveillance strategies for patients with HTAD 2.