Rasgrp1, a Ras guanine nucleotide exchange factor, is an essential regulator of lymphocyte receptor signaling. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor, activating RAS by exchanging bound GDP for GTP, with downstream effects at the cellular level [4]. Genetic models, like mouse models, have been crucial for studying its functions.

In mice, Rasgrp1 deletion leads to defective T lymphocyte development [1]. Rasgrp1 -deficient patients suffer from immune deficiency, and its gene has been linked to autoimmunity. Diminished Rasgrp1 expression in C57BL/6 mice causes defective T lymphocyte selection, and the severity of inflammatory disease inversely correlates with its expression levels [1]. In psoriasis mouse models, Rasgrp1 deficiency and overexpression influence imiquimod-induced psoriasis-like manifestations and skin inflammation, as VEGF mediates psoriatic inflammation through the RasGRP1 -AKT -NF-κB pathway [2]. Also, RasGRP1 promotes the acute inflammatory response by sponging let -7a to increase IL-6 expression at the mRNA level, and restricts inflammation-associated cancer cell growth by disrupting the EGFR -SOS1 -Ras -AKT signaling pathway at the protein level [3].

In conclusion, Rasgrp1 plays a vital role in lymphocyte receptor signaling, T lymphocyte development, and immune-related processes. Mouse models with Rasgrp1 knockout or conditional knockout have revealed its significance in autoimmunity, psoriasis, and the regulation of the acute inflammatory response and inflammation-associated cancer, contributing to our understanding of these disease areas.