Mapk1, also known as mitogen-activated protein kinase 1, is a key component of the MAP kinase signal transduction pathway. It has functions both as a kinase, phosphorylating histones, and as a transcription factor, directly binding to gene promoter regions to regulate gene expression. This dual-role protein is involved in multiple biological processes and is crucial for cell survival, proliferation, and response to various stimuli [2].

In breast cancer, phosphorylation of ULK1 by MAPK1/ERK2-MAPK3/ERK1 kinase triggers ULK1's interaction with BTRC, leading to its K48-linked ubiquitination and proteasome degradation. ULK1 deficiency, due to MAPK1-mediated degradation, attenuates mitophagy, activates the NLRP3 inflammasome, and promotes breast cancer bone metastasis [1].

In gastric cancer, MAPK1 promotes cell invasion and migration by bidirectionally regulating target genes as a transcription factor [2].

In diabetic kidney disease, high glucose increases MAPK1, which reduces PACS-2 levels, disrupts the mitochondria-associated endoplasmic reticulum membrane (MAM), and causes mitochondrial fragmentation. Inhibition of MAPK1 in diabetic mice increases PACS-2 and protects against MAM loss and mitochondrial fragmentation [3].

In pancreatic cancer, SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, facilitating pancreatic cancer growth and metastasis [4].

In bladder cancer, circPSMA7 acts as a sponge for miR-128-3p, increasing MAPK1 expression and promoting cancer progression [5].

In prostate cancer, miR-92a-1-5p enriched extracellular vesicles regulate osteoclast function via reduction of MAPK1 [6].

In osteosarcoma, circ_0020378 promotes cell proliferation and migration by regulating the miR-556-5p/MAPK1 axis [7].

In cervical cancer, LINC00511 promotes cancer progression by regulating the miR-497-5p/MAPK1 axis [8].

In Leishmania donovani, MAPK1 modulates the expression levels of various phosphoproteins involved in metabolism, signal transduction, etc., which are crucial for parasite survival, infectivity, etc. [9].

In glioblastoma, SNHG12 sponges miR-129-5p, leading to upregulation of MAPK1 and endowing cells with temozolomide resistance [10].

In conclusion, Mapk1 plays diverse and crucial roles in multiple biological processes and disease conditions. Through gene-knockout or conditional-knockout mouse models and other functional studies, it has been revealed that Mapk1 is involved in cancer metastasis, cell invasion, mitochondrial function in diabetes-related diseases, and parasite survival. Understanding the functions of Mapk1 provides insights into disease mechanisms and potential therapeutic targets for various diseases such as cancer and diabetic kidney disease.