Gpsm1, also known as activator of G-protein signaling 3, is an accessory protein that modulates G-protein signaling. It is involved in multiple pathways such as Gαi3/cAMP/PKA/CREB axis, which impacts various biological processes like cell proliferation, apoptosis, and immune-related responses, making it biologically important [1,3,4]. Genetic models, especially KO/CKO mouse models, have been crucial in studying Gpsm1's functions.

In myeloid-specific Gpsm1-ablated mice, they are protected against high-fat-diet-induced insulin resistance, glucose dysregulation, and liver steatosis as Gpsm1 deficiency promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, inhibiting TLR4-induced NF-κB signaling in macrophages, indicating its role in metabolic inflammation [1]. Mice lacking Gpsm1 in POMC neurons are protected against diet-induced obesity, glucose dysregulation, etc. as Gpsm1 deficiency in these neurons enhances autophagy and leptin sensitivity through PI3K/AKT/mTOR signaling, increasing POMC expression and related processes [2]. In an orthologous mouse model of autosomal dominant polycystic kidney disease, complete loss of Gpsm1 led to increased cyst progression and reduced renal function, suggesting its role in controlling cyst dynamics [5].

In conclusion, Gpsm1 is essential in regulating metabolic homeostasis, energy balance, and cyst progression in diseases. Studies using Gpsm1 KO/CKO mouse models have significantly contributed to understanding its role in metabolic diseases like type 2 diabetes and obesity, as well as in autosomal dominant polycystic kidney disease.