Mark1, also known as microtubule affinity regulating kinase 1, is involved in regulating microtubule-related functions. It has been implicated in multiple biological processes and diseases. The kinase associated-1 (KA1) domain at its C-terminus is involved in its autoinhibition, potentially blocking peptide substrate binding [6].

In vivo studies using gene knockout models have revealed significant functions of Mark1. Forebrain-specific conditional knockout (cKO) of Mark1 in mice leads to defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons, with reduced spine density. These cKO mice also show synaptic accumulation of GKAP and GluA2 (or GluR2), as well as defects in spatial learning in the Morris water maze and reduced anxiety-like behaviors, suggesting its role in cognitive functions [1,2].

In lung development, Mark1-knockout (KO) mice exhibit impaired distal sacculation and type I pneumocyte (AECI) flattening. Fibroblasts expressing Mark1 are required for the terminal stages of pulmonary development, and Mark1-mediated fibroblast activation induces AECI flattening [3].

In hepatocellular carcinoma, MARK1 mRNA expression is decreased, and overexpressing it suppresses sorafenib-induced proliferation in resistant cells by negatively regulating POTEE [4].

In cervical tumor cells, MARK1 is a target of miR-125a-5p, and its inhibition by the miRNA enhances cell migration [5].

In colorectal cancer, miR-23a promotes cell proliferation and migration by down-regulating MARK1 [7].

In conclusion, Mark1 plays crucial roles in neurodevelopmental processes like dendritic spine morphogenesis and cognitive functions, lung development, and in the context of several cancers. Gene knockout and conditional knockout mouse models have been instrumental in uncovering these functions, providing insights into the biological mechanisms and potential therapeutic targets for related diseases.