Serine/threonine-protein kinase STK11

STK11 (serine/threonine-protein kinase LKB1) is a tumor suppressor kinase that functions as a master regulator of AMP-activated protein kinase (AMPK) family members (UniProt: Q15831). The protein phosphorylates and activates multiple AMPK-family kinases including PRKAA1, PRKAA2, BRSK1, and BRSK2, thereby controlling cellular metabolism, polarity, apoptosis, and DNA damage responses. STK11 additionally regulates neuronal polarization and axon specification through BRSK1/2 activation.

STK11 is expressed broadly and plays roles in glucose homeostasis, autophagy regulation, and cortical neuron development (UniProt: Q15831). In the germline and testis, it contributes to spermiogenesis. UniProt documents associations with Peutz-Jeghers syndrome (MIM 175200) and testicular germ cell tumor (MIM 273300), both linked to STK11 loss-of-function mutations.

In Alzheimer's disease, STK11 protein levels are significantly reduced in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.35 across measured fractions, indicating downregulation. This decrease may reflect compromised energy metabolism and autophagy pathways central to neurodegeneration, given STK11's role as an upstream AMPK activator.