Protein targets & therapeutics in psoriasis: toward personalization

Over 125 million individuals worldwide suffer from psoriasis, a chronic inflammatory skin condition that is immune-mediated. It is often linked to systemic comorbidities such psoriatic arthritis, cardiovascular disease, and mental health conditions. It is characterised by erythematous plaques, itching, and scaling. Psoriasis is caused by a complex interaction of environmental factors, genetic predisposition, and dysregulated immune responses, which leads to chronic inflammation and keratinocyte hyperproliferation. This review examines the treatment potential of important protein targets linked to psoriasis. Transcriptional regulators that affect inflammatory cascades and immune cell behavior include ACKR2, NFKBIZ, and TNIP1. Proteins like PK2 and KPNA2 affect the growth and differentiation of keratinocytes, and kynurenine pathway enzymes like KYNU and IDO lead to immunological imbalance. Inflammatory mediators like CXCL10 and CYR61, as well as antimicrobial peptides like LL37 and S100A15, are significantly increased in psoriatic lesions and maintain the chronic inflammatory state. Using information from the Protein Data Bank (PDB), the review also looks at the structural biology of these proteins, providing insights into molecular interactions and drug-binding sites. The study highlights the importance of these proteins in promoting individualised psoriasis treatment by combining molecular targeting techniques with new biologic treatments. This review surveys molecular proteins implicated in psoriasis, focusing on their potential as biomarkers or therapeutic targets. While many, such as CXCL10 or S100A15, are broadly involved in inflammatory cascades, others like LL37, TNIP1, and RORγt exhibit roles more uniquely tied to psoriatic pathology and may underpin future personalized treatment approaches.