LRRC1 is a regulator of cellular polarity that is expressed at high levels in a range of tumor tissue types. Here, we conducted an analysis of the previously unexplored role of LRRC1 as a component of the adipogenic differentiation network. During the early stage (days 3–7) adipocytic differentiation of human mesenchymal stem cells (MSCs), LRRC1 was found to be upregulated at both the mRNA and protein levels. Moreover, the expression of LRRC1 was found to be controlled by PPARγ, which is a key transcriptional regulator of adipogenesis. Inhibiting LRRC1 expression reduced the adipogenic potential of hMSCs, with a concomitant reduction in the expression of three adipogenesis-associated proteins (SCD, LIPE, FASN). Together, these data offer new insight into the functional importance of LRRC1 both in general and in the context of adipocytic differentiation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11010-022-04609-8.