Med22, a subunit of the Mediator complex, is crucial for gene transcription as the Mediator connects transcriptional regulators and RNA polymerase II [4]. The Mediator head module, which includes Med22, is involved in the recruitment of TFIIH and TFIIE to the preinitiation complex, playing a role in the regulation of gene expression [6].

Podocyte-specific Med22 knockout mice revealed that while Med22 is not essential for normal podocyte maturation, it is critical for maintaining podocyte health. Its deficiency leads to intracellular vacuole formation, podocyte loss, progressive glomerular disease, and ultimately death due to renal failure, suggesting a role in the development of glomerulopathies [1].

In patients with major depressive disorder, genetic and environmental components of MED22 expression regulation are associated with childhood trauma, and its genetic variations are linked to higher neuroticism in healthy volunteers. Moreover, trauma-focused psychotherapy decreases MED22 expression, and baseline levels are associated with relapse, indicating its potential role in detecting relapse [2].

In bladder cancer, MED22 was identified as a potential new pharmaceutical target when analyzing THZ1-sensitive and super-enhancer-associated oncogenes [3].

In Drosophila spermatocytes, loss of Med22 function causes meiosis I maturation arrest and male infertility, similar to the loss of function of other related complexes, suggesting its role in the regulation of genes required for spermatid differentiation [5].

In summary, Med22 plays essential roles in maintaining podocyte health, is associated with major depressive disorder, and may serve as a potential target in bladder cancer. In Drosophila, it is crucial for spermatid differentiation. Gene-knockout models, especially in mice, have been instrumental in uncovering these functions, providing valuable insights into the biological processes and disease conditions related to Med22.