Dnajb6, also known as mammalian relative of DnaJ (MRJ), is a ubiquitously expressed Hsp40 co-chaperone. It contains a J domain that specifies Hsp70 functions in the cellular environment. Dnajb6 is involved in diverse cellular functions such as preventing the aggregation of mis-folded proteins, which is crucial for maintaining proteostasis. It also plays a role in processes like murine placental development and the self-renewal of neural stem cells. Its dysfunction is associated with multiple pathologies including limb-girdle muscular dystrophy, neurodegenerative diseases, and cancer [1,3,4].

In limb-girdle muscular dystrophy type 1D (LGMD1D), mutations in Dnajb6 lead to abnormal protein aggregates and rimmed vacuoles in muscle fibers. Conditional muscular expression of a Dnajb6 mutant in mice causes an LGMD1D myofibrillary muscle tissue phenotype, revealing its role in maintaining muscle fiber integrity [1]. In the context of nuclear pore complex (NPC) biogenesis, loss of Dnajb6 results in the accumulation of cytosolic annulate lamellae, suggesting its importance in the quality control during NPC formation [2].

In conclusion, Dnajb6 is essential for various cellular functions, especially in maintaining protein homeostasis. The use of KO/CKO mouse models has significantly contributed to understanding its role in muscle-related diseases like LGMD1D and in NPC biogenesis. These insights may open up new therapeutic strategies for Dnajb6-related pathologies.