Mu-crystallin (Ketimine reductase) (CRYM)

Mu-crystallin (CRYM), also known as ketimine reductase, is a multifunctional cytoplasmic protein that plays a dual role as an enzyme and a high-affinity thyroid hormone-binding protein [1, 2, 8]. As an enzyme, it catalyzes the NADP(H)-dependent reduction of cyclic ketimines, such as those derived from the lysine degradation pathway (e.g., Δ1-piperideine-2-carboxylate), which is particularly important in the brain [3, 10, 16]. Concurrently, it binds triiodothyronine (T3) and thyroxine (T4) with high affinity, effectively sequestering these hormones in the cytoplasm and regulating their availability for nuclear thyroid hormone receptors [7, 12, 15]. Genetic mutations in the CRYM gene are a known cause of autosomal dominant nonsyndromic deafness (DFNA40), likely due to disrupted thyroid hormone homeostasis and potassium recycling in the cochlea [6, 13, 15]. In oncology, CRYM is often downregulated in aggressive prostate cancer, where it normally acts as an antagonist to thyroid and androgen receptor signaling [7]. Its expression levels also influence skeletal muscle plasticity and metabolism, making it a target of interest for muscle-wasting diseases and metabolic disorders [11, 14].

Other names

Ketimine reductaseMu-crystallinNADP-regulated thyroid hormone-binding proteinTHBPCRYMP2C/Pyr2C reductase1-piperideine-2-carboxylate/1-pyrroline-2-carboxylate reductase

Binding and sequestration of triiodothyronine (T3) in the cytoplasm to regulate its availability for nuclear receptors; NADP-dependent reduction of cyclic ketimines in the pipecolic acid pathway.