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Its hallmark, cryptic exon (CE) splicing, is often masked in bulk tissue analyses by the low abundance of affected neurons. We developed an ultrasensitive RT\u2010qPCR assay targeting\n                    <jats:italic>STMN2<\/jats:italic>\n                    CE using one exon\u2013CE junction\u2010spanning primer and the other within the CE. The design expands the dynamic range sevenfold: TDP\u201043 knockdown boosted\n                    <jats:italic>STMN2<\/jats:italic>\n                    CE levels 1395\u2010fold in differentiated SH\u2010SY5Y neurons. Spike\u2010in tests set detection at 0.16% deficient cells. Crucially, the assay revealed a 42\u2010fold CE increase in ALS motor cortex, previously missed by conventional primers. This streamlined tool enables precise quantification of TDP\u201043 dysfunction and sensitive pharmacodynamic monitoring for future ALS\u2010FTD therapeutic studies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>\n                        Because cryptic\u2010exon signals are diluted in bulk tissue, we developed a junction\u2010spanning\n                        <jats:italic>STMN2<\/jats:italic>\n                        RT\u2010qPCR with sub\u2010percent sensitivity. This deployable biomarker will aid ALS\/FTD researchers and drug developers by standardizing measurements and enabling sensitive pharmacodynamic monitoring of therapies targeting nuclear TDP\u201043 dysfunction.\n                      <\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70198","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T07:10:17Z","timestamp":1761117017000},"page":"119-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Quantifying subpercent nuclear\n                    <scp>TDP<\/scp>\n                    \u201043 loss in cells and\n                    <scp>ALS<\/scp>\n                    cortex using junction\u2010specific cryptic exon\n                    <scp>RT<\/scp>\n                    \u2010\n                    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