Background: In rheumatoid arthritis, an inflammatory illness affecting the immune system, the synovial membrane may grow and eventually destroy bone and cartilage in the joints. This study set out to quantify CST5 in RA patients and look for any associations between the protein and measures of disease activity and severity. Methods: For six months, researchers at Benha University Hospitals' Rheumatology, Rehabilitation, and Physical Medicine outpatient clinic and inpatient department tracked 43 patients with rheumatoid arthritis (RA). Participants were randomly assigned to one of two groups based on their perceived health status. Group A consisted of 43 participants of similar age and sex, while group B served as a control. Findings: CST5 levels were noticeably greater in RA patients when compared with controls (p < 0.001 for all). Compared to healthy controls, rheumatoid arthritis patients had significantly higher CST5 levels (median 4.8 ng/ml). Disease activity categories did not substantially affect CST5 levels. The connection between CST5 and ESR was negative and statistically significant (r=-0.327, p=0.03). The CST5 assay demonstrated excellent sensitivity (88.4%), specificity (84.7%), and area under the curve (0.917) for the diagnosis of RA at a cutoff of 2.90 ng/ml. Bottom line: CST5 levels are much higher in RA patients and are associated with several indicators of disease activity. Given its excellent diagnostic accuracy, CST5 has the potential to become an invaluable asset in the arsenal of biomarkers used for the treatment of RA.