Transferrin receptor (TfR) is overexpressed on the surface of many cancer cells due to its vital roles in iron circulation and cellular respiration. Soluble transferrin receptor (sTfR), a truncated extracellular form of TfR in serum, is an important marker of iron deficiency anemia (IDA) and bone marrow failure in cancer patients. More recently, sTfR level in urine has been related to a specific kidney disease of Henoch-Schönlein purpura nephritis (HSPN). Despite the universal significance of sTfR, there is still a lack of a simple and sensitive method for the quantification of sTfR. Furthermore, it is desirable to have a probe that can detect both TfR and sTfR for further comparison study. In this work, we developed a water-soluble AIE-peptide conjugate with aggregation-induced emission (AIE) characteristics. Taking advantage of the negligible emission from molecularly dissolved tetraphenylethene (TPE), probe TPE-2T7 was used for the light-up detection of sTfR. The probe itself is nonemissive in aqueous solution, but it turns on its fluorescence upon interaction with sTfR to yield a detection limit of 0.27 μg/mL, which is much lower than the sTfR level in IDA patients. Furthermore, a proof-of-concept experiment validates the potential of the probe for diagnosis of HSPN by urine test.