A certain period of time before the events of Ōkamiden, Ayame was diagnosed with a terminal disease that would be fatal, so she and her mother moved to Yakushi Village in order to seek for treatments.
Ayame was first encountered when Chibiterasu was exploring Yakushi Village upon his arrival in Nippon. However, due to her lack of belief in the gods, she saw Chibiterasu as a mere white wolf puppy, and showed no interest. She is not seen until much later in the storyline, when Yakushi Village is revisited, with Kuni accompanying Chibiterasu. As they entered the village, Ayame was found collapsed on one of the bridges. After she recovered, she told the duo that she has a terminal illness that currently has no possible cures, and she would die within a year. Knowing that she could not accomplish much in such a short time, her last wish was to see one of Tama's firework shows, but unfortunately, the pyrotechnist had caught a serious illness and was incapacitated, while Dr. Redbeard refused to give him any medications due to a personal grudge regarding Tama stealing his herbs for experimenting on firework colors, which he saw as completely pointless and unbearably loud . However, upon knowing that Ayame's last wish before the end of her life was to see a firework show of Tama's, the apothecary was deeply moved, and gave Kuni and Chibiterasu the dose of medication needed to cure Tama's illness, as well as the herbs that he needed for his fireworks. Ayame was at great delight upon seeing Tama's famous firework show, and hoped that she could see such an event once again.
Much later in the storyline, after the defeat of King Fury, Dr. Bluebeard gave Chibiterasu and Kagu some fungi, per his promise for a reward to them when they caught a boy trying to steal some of his medicine. These fungi, when combined with Dr. Redbeard's herbal medicine, formed a very potent solution that could cure Ayame's terminal illness. Fortunately, just as her disease was about to take her life, Dr. Bluebeard's fungi was delivered in time, and the formed solution cured Ayame of her illness. Now rid of her life-threatening illness, Ayame could live a normal life and travel wherever she wanted to, including the capital. Everyone then watched another firework show of Tama's to celebrate this miracle.
Ayame wears an orange kimono decorated with imprints of gourds, with a dark pink obi. She has a necklace comprised of a gourd pierced through the upper half by a string, possibly holding medicine for emergency usage. She has black, medium length hair that is tied into two short buns at the back, with multiple bangs on the front covering her forehead and round face with blushes. Also on the back of her head is an orange flower ornament.