Ldlrad4, or low-density lipoprotein receptor class A domain-containing protein 4, is a gene with implications in multiple biological processes and diseases. Structurally, its protein is similar to TMEPAI, which is overexpressed in many tumors. It is involved in regulating the TGF-β signaling pathway and may play a role in lipid metabolism [3,5].

In cancer research, downregulation of Ldlrad4 in the liver of rats treated with nongenotoxic hepatocarcinogens induced TGF-β signaling, promoting cell proliferation and suppressing apoptosis in early hepatocarcinogenesis [2]. In contrast, in hepatic cancer cells, increased expression of Ldlrad4 promoted cell proliferation and migration, and its interaction with Nedd4 was shown to be important for these effects [3]. In colorectal cancer, the antisense lncRNA LDLRAD4-AS1 could decrease the expression of Ldlrad4, promoting metastasis through epithelial-to-mesenchymal transition [1]. In primary gastrointestinal stromal tumors, LDLRAD4 expression was an independent prognostic factor for recurrence-free survival [4].

In conclusion, Ldlrad4 has complex functions in different tissues and diseases, especially in cancer. Its role in regulating TGF-β signaling and cell behaviors such as proliferation, apoptosis, and metastasis is crucial. Studies, though not specifically from KO/CKO mouse models in the provided references, still reveal its significance in understanding disease mechanisms, which may potentially guide future research in developing targeted therapies for related diseases.