Evolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders

Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its housekeeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis, it performs a variety of noncanonical roles, mostly in CNS development. In the past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons. Many neurological disorders that differ in their etiology are commonly associated with aberrant levels of Calreticulin, that lead to modulation of apoptosis and phagocytosis, and impact on transcriptional pathways, impairment in proteostatis, and calcium imbalances. Such multifaceted properties of Calreticulin are the reason why it has been implicated in vital roles of the nervous system in recent years. Hence, understanding its role in the physiology of neurons would help to unearth its involvement in the spectrum of neurological disorders. This Review aims toward exploring the interplay of Calreticulin in neurological disorders which would aid in targeting Calreticulin for developing novel neurotherapeutics.