Heat shock protein HSP27 was shown to be its major direct substrate in vivo.

[8] MK2 pathway has been demonstrated to have a key role in maintaining and repairing the integrity of endothelial barrier in the lung via actin[9] and vimentin remodeling.

Activation of MK2 via its phosphorylation by p38 has been shown to restore the vascular barrier[7] and repair vascular leak,[10] associated with over 60 medical conditions, including Acute Respiratory Distress Syndrome (ARDS), a major cause of death around the world.

[11] MAPKAPK2 mediates the initiation of the senescence-associated secretory phenotype (SASP) by mTOR (mechanistic target of rapamycin).

[12][13] Interleukin 1 alpha (IL1A) is found on the surface of senescent cells, where it contributes to the production of SASP factors due to a positive feedback loop with NF-κB.