YKL-06-061 is a potent and selective SIK (salt-inducible kinase) inhibitor. Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). Salt-inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification. Pharmacologic inhibition of SIK sends HDAC4 to the nucleus and inhibits the calcification process in VSMCs, aortic rings, and in vivo In the cytoplasm, HDAC4 binds and its activity depends on the adaptor protein ENIGMA (Pdlim7) to promote vascular calcification.