Mpzl3, or Myelin Protein Zero-Like 3, is a nuclear-encoded, mitochondrially localized, immunoglobulin-like V-type protein. It functions as a key regulator in multiple biological processes, including epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, energy expenditure, sebaceous gland function, and hair follicle cycling [1]. It may also be part of signaling pathways regulated by core clock gene products and/or PPARγ [1]. Genetic models, especially mouse models, are valuable for studying its functions.

In Mpzl3 knockout mice, various phenotypes have been observed. They show unkempt and greasy hair, hair loss, severe sebaceous gland hypertrophy, increased dermal thickness, and frequently develop inflammatory skin lesions, resembling a seborrheic dermatitis-like phenotype [4,5]. Loss of Mpzl3 function also causes a significant reduction in cutaneous and overall adipose tissue [4]. Antisense oligonucleotide-mediated knockdown of Mpzl3 in diet-induced obese mice can attenuate negative metabolic effects like reducing fat mass and circulating lipids [3]. In addition, in MET-amplified cancer cells, MPZL3, as a HER3-dependent effector, plays an oncogenic role in the HER3-MPZL3 axis [2].

In summary, Mpzl3 plays essential roles in skin development, hair growth, adipose cell functions, and metabolism. The Mpzl3 knockout mouse models have been crucial in revealing its functions in seborrheic dermatitis-related phenotypes, obesity-associated metabolic regulation, and cancer-related cell proliferation, providing insights into the underlying mechanisms of these disease conditions.