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In IDD, the most affected component of the intervertebral disc is the nucleus pulposus (NP). Derived from the notochord, where cells are organized into a tandem configuration, young NP cells cluster in three\u2010dimensional (3D) networks embedded in a gelatinous matrix. Here, we review the current understanding of NP development, homeostasis, physiology, and degeneration with a focus on the roles of the cell adhesion molecule N\u2010cadherin in these processes. Based on the literature, we hypothesize that N\u2010cadherin contributes to the architectural transition from the notochord to the NP by mediating a switch in cellular organization from tandem to random orientational cell adhesions (OCAs). We further hypothesize that the 3D clustering of NP cells may facilitate N\u2010cadherin to act as a mechanosensor to modulate NP gene expression under mechanical stresses. We hope these hypotheses promote future research on the etiology of human IDD and the development of measures to prevent and treat IDD. Some open questions on N\u2010cadherin functions in the NP are also discussed.<\/jats:p>","DOI":"10.1111\/brv.70081","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T07:17:52Z","timestamp":1758266272000},"page":"268-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The tandem\u2013random transition of cellular patterning: proposed roles of N\u2010cadherin\u2010based orientational cell adhesions in the development, maintenance, and degeneration of the nucleus pulposus"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4559-8707","authenticated-orcid":false,"given":"Xiangyun","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Department of Microbiology &amp; Molecular Genetics University of Pittsburgh  1622 Locust Street Pittsburgh PA 15219 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, McGowan Institute for Regenerative Medicine, and Department of Pathology University of Pittsburgh  200 Lothrop Street Pittsburgh PA 15261 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwendolyn A.","family":"Sowa","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Department of Orthopaedic Surgery, and Department of BioEngineering University of Pittsburgh  3471 5th Avenue Pittsburgh PA 15213 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