Table 6.

Key Molecular Pathways Altered by WFS1 Dysfunction.

Molecular Pathway	Normal Role of WFS1	Effect of WFS1 Dysfunction
Unfolded Protein Response	Maintains ER homeostasis, regulates UPR sensors (ATF6, IRE1, PERK)	Chronic ER stress, prolonged UPR, increased apoptosis
Calcium Homeostasis	Controls ER calcium levels and signaling between ER and mitochondria	Calcium dysregulation, excitability, mitochondrial dysfunction
Mitochondrial Function	Supports ER–mitochondria communication for ATP production	Impaired ATP production, oxidative stress, ROS increase
Autophagy and Protein Clearance	Prevents protein aggregation via proper folding and degradation	Misfolded proteins, amyloid-β plaques, tau tangles
Dopaminergic Signaling	Modulates neurotransmitter release and neuronal excitability	Altered release, excitability, sleep disturbances
Neuroinflammation	Mitigates stress-induced inflammation	Activation of inflammatory pathways, cytokine release

The table outlines the normal roles of WFS1 across various molecular pathways and the effects of its dysfunction, emphasizing the pathological changes found in conditions related to WFS1 impairment [12,22,23,25,28].