Prkd2, encoding the serine/threonine kinase protein kinase D2, is involved in multiple biological processes. It has been implicated in pathways such as Notch1, TP53/CDKN1A, and is crucial for the tumor-supporting activity of HSP90, also playing roles in T follicular helper cell differentiation, insulin secretion, and bone and glucose metabolism [1-5, 7, 10]. Genetic models, like KO mouse models, are valuable for studying its functions.

In AML, knockdown of Prkd2 induced apoptosis and increased chemosensitivity, indicating it promotes AML cell proliferation and chemoresistance via regulating Notch1 pathway [1]. In cervical cancer, Prkd2 knockdown increased chemotherapy sensitivity through the TP53/CDKN1A pathway [2]. In Prkd2 -/- mice, there was excessive TFH development due to unrestricted Bcl6 nuclear translocation, as Prkd2 and Bcl6 form a mutually inhibitory loop controlling TFH cell differentiation [3]. PRKD2-KO mouse model showed that its deletion triggers hyperinsulinemia preceding IR and metabolic disorders, as it promotes β-cell insulin secretion [4].

In conclusion, Prkd2 plays essential roles in cell proliferation, chemoresistance in cancer, T cell differentiation, and metabolic regulation. Studies using KO mouse models have revealed its significance in AML, cervical cancer, T follicular helper cell function, and metabolic diseases, providing insights into disease mechanisms and potential therapeutic targets.