He was active in the region of Macedonia, and was widely considered to be the most prominent and influential figure of the palaeologan renaissance and the Macedonian school of painting centered at the Empire's second-largest city, Thessaloniki.

His works can be found in several monasteries of Mount Athos: Vatopedi, Megisti Lavra, and the Protaton Church in Karyes.

[4] A 2024 handwriting analysis conducted on Panselinos' Protaton mural painting matched his handwriting with lettering on Marcian Codex GR 516, a manuscript attributed to Macedonian school painter Ioannis Astrapas, a relative of Michael and Eutychios Astrapas.

Father Cosmas Simonopetritis, a former Mount Athos administrator, has suggested that Manuel Panselinos was a nickname adopted by Astrapas for his work.

[5] Stylistically, art historians have pointed out a distinctive style in Manuel's works and striking similarities between various paintings attributed to him: their soft colors, the symmetrical rendering of the figures, and the uniqueness of form in compositions and proportions, especially in faces.