Genital endometriosis is a chronic multisystem disease in which pain syndrome remains the leading clinical manifestation. Despite significant advances in understanding the pathogenesis of endometriosis, the mechanisms of pain generation and the reasons for the discrepancy between the extent of morphological lesions and the severity of clinical symptoms remain the subject of active investigation. In recent years, increasing attention has been paid to the role of nerve fibers and neuroimmune interactions in the development of endometriosis-associated pain. The aim of this review is to analyze current data on the role of protein gene product 9.5 (PGP 9.5) as an immunohistochemical marker of nerve fibers in the pathogenesis of pain syndrome and in the diagnosis of endometriosis. The review addresses contemporary concepts of neuronal and neuroimmune mechanisms of pain, features of innervation of the eutopic endometrium and endometriotic lesions, as well as the potential for nerve fiber detection using PGP9.5. Particular emphasis is placed on data regarding the association between nerve fiber density and pain severity, as well as on the prospects for the use of this marker in minimal and early forms of the disease. The analysis of the literature indicates that PGP9.5 is a sensitive and biologically substantiated marker reflecting the neuronal component of endometriosis. At the same time, its use in clinical practice is limited by methodological heterogeneity among studies, the lack of standardized protocols for quantitative assessment, and the absence of universal diagnostic thresholds. At present, PGP9.5 should be regarded as an auxiliary and research tool, the application of which is feasible within comprehensive diagnostic algorithms. Further studies aimed at standardizing methodologies and validating diagnostic criteria are required to clarify the clinical relevance of this approach.