Lmbrd1, also known as limb region 1 (LMBR1) domain containing 1 gene, encodes a lysosomal membrane protein LMBD1. It is crucial for vitamin B₁₂ metabolism, specifically facilitating lysosomal cobalamin export. Mutations in Lmbrd1 lead to the cblF defect, disrupting cobalamin coenzyme synthesis and causing disorders related to methionine and methylmalonyl-coenzyme A metabolism [1,4].

Lmbrd1-deficient mice generated using the Cre/LoxP system showed that complete loss of Lmbrd1 function leads to early embryonic death. Studies on these mice revealed that the initial formation of the proximal-distal axis is unaffected, but the initiation of gastrulation is disturbed [2]. Heterozygous knockout mice (Lmbrd1+/-) exhibited increased cardiac-glucose uptake, cardiac hypertrophy, ventricular tissue fibrosis, elevated heart rate, and enhanced cardiac muscle contractility. As they aged, signs of ventricular function deterioration were observed, suggesting Lmbrd1's role in mediating cardiac energy homeostasis and regulating cardiac function [3].

In conclusion, Lmbrd1 is essential for processes like gastrulation during embryogenesis and for maintaining normal cardiac function. Studies using gene-knockout mouse models have provided insights into its role in these biological processes and the associated disease conditions such as cobalamin-related disorders and cardiac diseases.